Isoforms of mouse serotonin 5-HT2c receptor

ABSTRACT

The invention includes mouse serotonin 5-HT2c receptor isoforms having amino acid replacements at one or more positions of the natural mouse serotonin 5-HT2c receptor polypeptide sequence, specifically at one or more of positions 157, 159 and 161. The polypeptides are useful for identifying ligands which bind with the serotonin 5-HT2c receptor and modulators of the serotonin 5-HT2c, and for identifying drugs with affinity for 5-HT2 receptors which are used to treat schizophrenia, Parkinsonism, and anxiety disorders.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of Ser. No. 09/526,309 filed onMar. 15, 2000 now U.S. Pat. No. 6,495,665 claims priority of U.S.provisional application Ser. No. 60/124,439, filed Mar. 15, 1999.

BACKGROUND OF THE INVENTION

Serotonin is a neuromodulator capable of inducing and modulating a widevariety of behavioral functions such as sleep, appetite, locomotion,sexual activity and vascular contraction. It is accepted that serotoninactivity is mediated by its interaction with receptors, designatedserotoninergic receptors of 5-HT (for 5-hydroxytryptamine) receptors.Molecular biology studies as well as pharmacological studies haverevealed the existence of a large number of subtypes of 5-HT receptors.The 5-HT receptors which have been described to date belong either tothe family of receptors associated with ion channels (5-HT3 receptors),or to the family of receptors which interact with G proteins and whichpossess seven transmembrane domains. Moreover, analysis of the aminoacid sequences has shown that the 5-HT receptors which interact with Gproteins may be subdivided into six distinct groups: 5-HT1 receptors,comprising the mammalian subtypes 5-HT1a, 5-HT1b, 5-HT1d, 5-HT1e and5-HT1f, as well as three Drosophila 5-HT receptors; 5-HT2 receptorscomprising three subtypes, 5-HT2a, 5-HT2b and 5-HT2c; 5-HT4 receptor;5-HT5 receptor; 5-HT6 receptor; and 5-HT7 receptor.

Drugs with affinity for 5-HT2 receptors are used to treat schizophrenia,Parkinsonism, and anxiety disorders. The 5-HT2c receptor subtype hasbeen particularly interesting to investigators searching for themolecular bases of neuropsychiatric disorders. The 5-HT2c receptor iswidely expressed in the brain where it is involved in regulatingendocrine responses. Particular responses include the production andsecretion of adrenocorticotropic hormone, oxytocin and prolactin. Genesfor mouse, rat and human (Saltzman et al., Biochem. Biophys. Res.Commun. 181:1469, 1991) 5-HT2c receptors have been cloned. Burns et al.,Nature vol. 387 15 May 1997 pp. 303-308 describes rat 5-HT2c receptorisoforms resulting from RNA editing events involving transcriptsencodong the serotonin receptor. The functional state of 5-HT2creceptors in normal controls and various patient groups has been studiedin vivo by administering 1-(3-chlorophenyl)piperazine (mCPP), anon-selective 5-HT2c agonist, and measuring hormonal and psychologicalresponses. In alcoholism, panic disorder, seasonal affective disorderand obsessive-compulsive disorder, mCPP has been shown to inducedifferent hormonal and psychological responses in patients and controls.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic representation of M2C/pE3 plasmid.

SUMMARY OF THE INVENTION

The invention includes mouse serotonin 5-HT2c receptor isoforms havingamino acid replacements at one or more positions of the previously knownmouse serotonin 5-HT2c receptor polypeptide sequence, specifically atone or more of positions 157, 159 and 161. The invention also includesisolated or purified isoforms, DNA encoding the isoforms, antibodieswith specific binding to the receptor isoforms, assays for detecting thereceptor isoforms, and expression vectors encoding the receptorisoforms.

DETAILED DESCRIPTION OF THE INVENTION

The invention includes an isolated polypeptide comprising a sequenceselected from the group consisting of (a) SEQ ID No. 3, (b) SEQ ID No.5, (c) SEQ ID No. 7, (d) SEQ ID No. 9, (e) SEQ ID No. 11, and (f)fragments of (a), (b), (c), (d), and (e) wherein the polypeptide hasserotonin activity. These polypeptides are mouse serotonin 5-HT2creceptor isoforms having amino acid replacements at one or morepositions of the previously known mouse serotonin 5-HT2c receptorpolypeptide sequence, specifically at one or more of positions 157, 159and 161.

The polypeptides are useful for identifying ligands which bind with theserotonin 5-HT2c receptor and modulators of the serotonin 5-HT2c, andfor identifying drugs with affinity for 5-HT2 receptors which are usedto treat schizophrenia, Parkinsonism, and anxiety disorders.

The invention also includes a method for identifying modulators of apolypeptide comprising a sequence selected from the group consisting of(a) SEQ ID No. 3, (b) SEQ ID No. 5, (c) SEQ ID No. 7, (d) SEQ ID No. 9,(e) SEQ ID No. 11, and (f) fragments of (a), (b), (c), (d), and (e),comprising contacting in the presence of 5-HTa molecule or a mixturecontaining different molecules with a recombinant cell expressing at itssurface a polypeptide of claim 1, under conditions permittinginteraction between the polypeptide and 5-HT, and detecting moleculescapable of modulating the activity of the polypeptide in the presence orabsence of 5HT.

The invention also includes isolated nucleotide sequences coding for apolypeptide comprising a sequence selected from the group consisting of(a) SEQ ID No. 3, (b) SEQ ID No. 5, (c) SEQ ID No. 7, (d) SEQ ID No. 9,(e) SEQ ID No. 11, and (f) fragments of (a), (b), (c), (d), and (e), orthe complementary strand, including such nucleotide sequences consistingof genomic sequences, cDNA sequences, RNA sequences, synthetic sequencesand semi-synthetic sequences. Also within the the invention are suchsequences placed under the control of signals permitting expression ofthe polypeptide in a host cell.

The invention also includes recombinant cells comprising nucleotidesequences of the invention, including eukaryotic and prokaryotic cells,and vectors for transforming the cells.

The invention also includes mammalian cell membranes comprising apolypeptide sequence selected from the group consisting of (a) SEQ IDNo. 3, (b) SEQ ID No. 5, (c) SEQ ID No. 7, (d) SEQ ID No. 9, (e) SEQ IDNo. 11, and (f) fragments of (a), (b), (c), (d), and (e) wherein thepolypeptide has serotonin receptor activity. Optionally, the mammaliancell membranes are free of other receptor proteins. The mammalian cellmembranes may be prepared from mammalian cells containing cDNA whichencodes any of the polypeptides. The mammalian cells are transfectedwith recombinant DNA comprising vector DNA and cDNA which encode thepolypeptides.

The invention also includes a method for identifying ligands of apolypeptide comprising a sequence selected from the group consisting of(a) SEQ ID No. 3, (b) SEQ ID No. 5, (c) SEQ ID No. 7, (d) SEQ ID No. 9,(e) SEQ ID No. 11, and (f) fragments of (a), (b), (c), (d), and (e),comprising contacting a molecule or a mixture containing differentmolecules with a recombinant cell expressing at its surface one of thepolypeptides, under conditions permitting interaction between thepolypeptide and the molecule, and detecting molecules bound to thepolypeptide.

The invention also includes a method for identifying modulators of apolypeptide comprising a sequence selected from the group consisting of(a) SEQ ID No. 3, (b) SEQ ID No. 5, (c) SEQ ID No. 7, (d) SEQ ID No. 9,(e) SEQ ID No. 11, and (f) fragments of (a), (b), (c), (d), and (e),comprising contacting in the presence of 5-HT a molecule or a mixturecontaining different molecules with a recombinant cell expressing at itssurface a polypeptide of claim 1, under conditions permittinginteraction between the polypeptide and 5-HT, and detecting moleculescapable of modulating the activity of the polypeptide in the presence orabsence of 5HT.

The present invention further includes antibodies specific for theserotonin receptor isoform proteins of the invention which do not bindto the receptor as described by Yu et al. in GenBank X72230.

The term “isolated” refers to material that is removed from its originalenvironment (e.g., the natural environment if it is naturallyoccurring). For example, a naturally-occurring polynucleotide orpolypeptide present in a living animal is not isolated, but the samepolynucleotide or DNA or polypeptide, separated from some or all of thecoexisting materials in the natural system, is isolated. Suchpolynucleotide could be part of a vector and/or such polynucleotide orpolypeptide could be part of a composition, and still be isolated inthat such vector or composition is not part of its natural environment.

The mouse serotonin 5-HT2c subtype cDNA isoforms were subcloned into theexpression vector pE3 which is modified as described below from pCEP4(Invitrogen, Carlsbad, Calif.). Transient expression in HEK293e cells(Invitrogen, Carlsbad, Calif.) was accomplished by transfection of thecloned receptor cDNAs under the control of a CMV promoter into mammaliancells (e.g., HEK293e cells). Membranes prepared from the transfectedcells are utilized for the determination of binding affinity,selectivity and specificity of the receptors for various ligands. Stableexpression of the receptors in mammalian cells (e.g., CHO, HEK 293) isachieved after integration of the transfected cDNA into the chromosomesof the host cells. These stable cell lines constituently express thecloned receptors and can be propagated infinitely. Stable cell linesexpressing the receptor cDNAs individually can be used in the bindingassay to measure the affinity and selectivity of the receptors forserotonin agonists, antagonists and enhancers. These cells can also beused in functional assay to determine the agonist activity of anyligand.

Membranes prepared from transfected (HEK 293e) cells were utilized in abinding assay to measure the affinity of the receptors for radiolabeledagonists, e.g. [3H]5HT or [3H]mesulergine. The binding assay wasperformed by incubating membranes with increasing concentrations ofradiolabeled agonists. Bound ligand was separated from free ligand byfiltration. Bound radioactivity was measured by scintillation counting.Substances which bind to or enhance binding to expressed receptors incells can be identified in competition binding assays with radiolabeledagonists. For the competition binding assay, membranes were incubatedwith a fixed concentration of radioligand and various concentrations ofunlabeled agonists or antagonists.

Functional assay was performed by loading the receptor-expressing with[3H]inositol, incubating the cells with a ligand and measuring theaccumulation of [3H]inositol trisphsophate inside the cells.

A transient expression system can be established by microinjection of invitro transcribed mRNA from the cloned receptor cDNAs into Xenopusoocytes. The expression system allows measurement of the biologicaleffects upon activation of the expressed receptors with ligand binding.

In the procedure for generating the isoforms of the present invention,transcripts encoding the mouse serotonin 5-HT2c receptor subtype undergoRNA editing events in which genomically encoded adenosine residues areconverted to inosines by the action of double-stranded RNA adenosinedeaminases (see Burns et al., Nature vol. 387 15 May 1997 pp. 303-308,which describes rat 5-HT2c receptor isoforms resulting from RNA editingevents involving transcripts encodong the serotonin receptor). Sequenceanalysis of complementary DNA isolates from dissected mouse brainregions have indicated the tissue-specific expression of new receptorisoforms encoded by distinct RNA species. Editing of 5-HT2c receptormessenger RNAs alters the amino acid coding potential of the predictedsecond intracellular loop of the receptor and can lead to alteredefficacy of the interaction between receptors and their G proteins. Asshown in Table 3, the 5HT EC₅₀ value is dependent on the amino acidsequence at position 157/159/161.

The table below compares a partial amino acid sequence of the publishedmouse serotonin 5-HT2c receptor (SEQ. ID No. 1) and the correspondingpartial nucleotide sequence of the published mouse serotonin 5-HT2creceptor RNA, with amino acid sequences and nucleotide sequencescorresponding to new isoforms of the mouse serotonin 5-HT2c receptor inthe location of sequence variation. The isoforms have amino acidsequences identical to the published mouse serotonin 5-HT2c receptorpolypeptide sequence except for specified amino acid replacements at oneor more positions of the published mouse serotonin 5-HT2c receptorpolypeptide sequence, specifically at one or more of positions 157, 159,and 161:

TABLE 1 Amino acid position SEQ. ID No. 157 158 159 160 161 1 (protein)Val Arg Ser Pro Val (RNA) GTG CGT AGT CCT GTT 3 (protein) Val Arg AsnPro Val (RNA) GTA/G CGT AAT CCT GTT 5 (protein) Val Arg Asp Pro Val(RNA) GTA/G CGT GAT CCT GTT 7 (protein) Val Arg Ser Pro Ile (RNA) GTA/GCGT AGT CCT ATT 9 (protein) Met Arg Asn Pro Ile (RNA) ATG CGT AAT CCTATT 11 (protein)  Ile Arg Asn Pro Val (RNA) ATA CGT AAT CCT GTT

Alternative isoforms within the scope of the invention, otherwiseidentical to the natural mouse serotonin 5-HT2c receptor, have thefollowing amino acid sequence and nucleotide sequence variations atpositions 157, 159 and 161:

TABLE 2 Amino acid position Sequence 157 158 159 160 161 a (protein) MetArg Asp Pro Val (RNA) ATG CGT GAT CCT GTT b (protein) Met Arg Asp ProIle (RNA) ATG CGT GAT CCT ATT c (protein) Met Arg Gly Pro Val (RNA) ATGCGT GGT CCT GTT d (protein) Met Arg Gly Pro Ile (RNA) ATG CGT GGT CCTATT e (protein) Met Arg Asn Pro Val (RNA) ATG CGT AAT CCT GTT f(protein) Ile Arg Asp Pro Val (RNA) ATA CGT GAT CCT GTT g (protein) IleArg Asp Pro Ile (RNA) ATA CGT GAT CCT ATT h (protein) Ile Arg Gly ProVal (RNA) ATA CGT GGT CCT GTT i (protein) Ile Arg Gly Pro Ile (RNA) ATACGT GGT CCT ATT j (protein) Ile Arg Asn Pro Ile (RNA) ATA CGT AAT CCTATT k (protein) Val Arg Asp Pro Ile (RNA) GTA/G CGT GAT CCT ATT l(protein) Val Arg Gly Pro Val (RNA) GTA/G CGT GGT CCT GTT m (protein)Val Arg Gly Pro Ile (RNA) GTA/G CGT GGT CCT ATT n (protein) Val Arg AsnPro Ile (RNA) GTA/A CGT AAT CCT ATT o (protein) Met Arg Ser Pro Val(RNA) ATG CGT ACT CCT GTT p (protein) Met Arg Ser Pro Ile (RNA) ATG CGTAGT CCT ATT

TABLE 3 5HT EC₅₀ values (nM) for vaious isoforms of mouse 5HT2c receptorSEQ ID No. Isoform 5HT EC₅₀ 1 VSV 3.5 3 VNV 3.1 5 VDV 5.9 9 MNI 0.9 11INV 1.6

EXAMPLE

Mouse brain cDNA (Clontech Catalog#7130-1) was used as a template toamplify the mouse 5HT2c receptor cDNA. The PCR oligos used in thisamplification were a sense oligo 5′-CTGAAGCAATAAATGGTGAACCTGGGCACTGwhich hybridizes to the start codon and several residues following thestart codon and an anti-sense oligo 5′-GCGTCTAGATTTCCTGTAGGAAAGCTGCGCTGwhich hybridizes to the 3′-untranslated region following the stop codon.The PCR product thus contains a mixture of the most abundant isoforms ofmouse 5HT2c receptor cDNA. To determine the sequence of mouse 5HT2creceptor cDNA, the PCR product was cut with XbaI restriction enzyme, andligated to the vector pE3 which was treated with the restriction enzymeStu I and XbaI.

The vector pE3 was modified from the pCEP4 vector (Cat# V044-50,Invitrogen, Carlsbad, Calif.) as described below. (1) To remove theeukaryotic expression cassete downstream of oriP segment (origin ofreplication from Epstein Bar virus), pCEP4 was digested with restrictionenzyme Xba I and Sal I, then blunt ended with the Klenow fragment of DNApolymerase and self-ligated with T4 DNA ligase. (2) To replace theEBNA-1 (Epstein-Barr virus nuclear antigen) upstream of the oriP segmentwith a eukaryotic expression cassete, the resulting plasmid from step 1was digested with restriction enzyme Xmn I and Sph I, and ligated withthe XmnI-XhoI DNA fragment from pcDNA3.1 kyg(+) (Invitrogen, cat #V870-20) containing CMV (cytomegalus virus) immediate early geneenhancer-promoter region and the Xho I-BamH I fragment from pCDM8(Invitrogen Cat # V308-20) containing the SV40 intron/poly A signal anda BamH I-Sph I linker. (3) The multiple cloning site was modified withsynthetic overlapping oligos containing unique sites of Sac I, Age I,Stu I , KpnI, Xho I, Sse8387 I, Not I and Xba I. Taken together, in thefinal plasmid pE3, EBNA-1 is deleted, the expression cassete is moved tothe upstream of oriP and transcription is in the same direction ofreplication.

After the mouse 5HT2c receptor PCR product has been ligated with the pE3vector, the ligation mixture was transformed into the E. coli host DH5α.Single colonies were picked from the transformation plate, followed byplasmid DNA preparation from each clone. The sequence of the mouse 5HT2creceptor cDNA was determined by standard fluorescence-based dideoxy DNAsequencing (Perkin-Elmer, Foster City, Calif.).

The plasmid carrying mouse 5-HT2c cDNA (abbreviated as m2C-pE3) wastransfected into 293-EBNA cells (Invitrogen, Cat # R620-07) by themethod of lipofection. Briefly, 2 μg plasmid DNA was diluted in 400 μlDulbecco's phophate-buffered saline and mixed with 30 μl lipofectaminereagent (GIBCO-BRL, cat # 10964-913). After 20 min incubation, themixture was diluted with 5 ml OPTI-MEM I reduced serum medium(GIBCO-BRL, cat #31985-013) and transferred to a T75 flask of 293-EBNAcells which were grown overnight. After 5-7 hr incubation at 37° C., thetransfection medium was aspirated off. The cells were washed twice withgrowth medium and cultured for 48 hr in CO₂ incubator. The cells werethen split and cultured in the medium containing 250 μg/ml hygromycin.The untransfected cells were killed, and the surviving cells collectedfor continuing culture or assaying.

A number of other cell lines are suitable for expressing mouse 5-HT2creceptors, such as CHO, HEK293, COS, or Hela cells. Transfection canalso be carried out by other methods, e.g. electroporation, calciumphophate precipitation, or DEAE-Dextran.

The recombinant 293-EBNA cells expressing mouse 5-HT2c receptors wereused in receptor binding and functional assays. To prepare membranes forbinding assays, the cells were homogenized in hypotonic buffer (50 mMTris-HCl, pH7.4, 5 mM MgCl₂). After removal of nuclei by low speedcentrifugation at 1000 g, the membranes were pelleted by centrifugationat 45,000 g for 30 min.

Ligand Binding Assays

Ligand binding assays are commonly used to determine how well a compoundbinds to a receptor. [3H]mesulergine or [3H] 5-HT binding assays werecarried out with the mouse 5HT2c membrane preparations. Radioligand wasincubated with the membranes in binding buffer (50 mM Tris-HCl, pH7.4, 5mM MgCl, 0.1% ascorbic acid and 10 uM pargylin) in the presense orabsense of unlabeled compounds. After 30 min incubation at roomtemperature, the binding reaction was terminated by filtering themixture through GF/C filters. After washing off the unbound ligand, theamount of radioligand-receptor complex trapped on the filter wasmeasured by scintilation counting. The binding affinities (Kd, IC₅₀ orKi) of the compounds for mouse 5-HT2c receptor could be calculated fromthe binding assays.

Functional Activity Assays

Second messenger assays are used to determine the functional activity ofa compound upon binding to a receptor. It is well established that5-HT2c receptor is coupled via G-protein of Gq/11 class tophosphatidyl-inositol (PI) hydrolysis resulting in the production of twosecond messengers, inositol trisphosphate (IP3) and diacylglycerol(DAG). The functional activity of mouse 5-HT2c receptor was determinedby measurement of the increases in the intracellular inositol phosphatelevel following agonist stimulation (PI assay). Transfected 293EBNAcells were seeded into multiwell plates and cultured in mediumcontaining [3H]-myo-inositol (2 uCi/ml) for 24-72 hr. After labellingperiod, cells were washed, and preincubated for 30 min in balanced saltbuffer containing 10 mM LiCl. Cells were then stimulated in the samebuffer with agonist 5-HT or test compounds for 45 min at 37° C. Afterremoval of the medium, the reaction was stoped by addition of 10 mMformic acid. Cell extracts were collected after 30 min incubation at 4°C., the inositol phosphate fraction was then isolated by anion exchangechromatography and quantitated by scintillation counting. The potency(EC50) and efficacy (% maximal response) of a compound activating mouse5-HT2c can be determined.

46 1 459 PRT VSV Transfected 293 Cells 1 Met Val Asn Leu Gly Thr Ala ValArg Ser Leu Leu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln PheAsp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe AsnSer Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln AsnTrp Pro Ala Leu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly GlyAsn Ile Leu Val Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu HisAsn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met LeuVal Gly Leu Leu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu TyrAsp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp IleSer Leu Asp Val Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu CysAla Ile Ser Leu Asp Arg Tyr Val Ala Val Arg Ser Pro 145 150 155 160 ValGlu His Ser Arg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175Ala Ile Val Trp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185190 Ile Gly Leu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195200 205 Val Leu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe210 215 220 Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr IleTyr 225 230 235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly HisThr Glu Glu 245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys CysCys Cys Lys Lys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro AsnPro Asp Gln Lys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro ArgGly Thr Met Gln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys ValLeu Gly Ile Val Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys ProPhe Phe Ile Thr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala CysAsn Gln Lys Leu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp IleGly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu PheAsn Lys Ile Tyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys AspTyr Lys Pro Asp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 ArgVal Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415Tyr Arg His Thr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425430 Pro Gly Ile Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435440 445 Ser Asn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 2 1380 DNAVSV Transfected 293 Cells 2 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcagt gcgtagtcct 480 gttgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 3 459 PRT VNV Transfected 293 Cells 3 Met ValAsn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15 GlyLeu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30 IleVal Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45 PhePro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60 IleIle Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 75 80Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 90 95Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100 105110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys 115120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser Ile Met130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Val Arg AsnPro 145 150 155 160 Val Glu His Ser Arg Phe Asn Ser Arg Thr Lys Ala IleMet Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val Ser ValPro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val Phe ValAsn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val Leu IleGly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met Val IleThr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln Thr LeuMet Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn Ile SerLeu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu Glu GluAsn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg Lys LysLys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn Asn GluLys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320 PheLeu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330 335Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340 345350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val 355360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys Tyr Leu370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg Gln IlePro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu AsnVal Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg Lys AlaAsn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn Leu GluLeu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile Ser SerVal 450 455 4 1380 DNA VNV Transfected 293 Cells 4 atggtgaacc tgggcactgcggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcg atatttccataagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtg gacgcttgtttcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtga ttataatcatgacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaaga aactgcacaatgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgg gactacttgtcatgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttac ctagatatttgtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatca tgcacctctgcgccatatcg ctggaccggt atgtagcagt gcgtaatcct 480 gttgagcata gccggttcaattcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaa taggagtttcagttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtga ataatactacctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcat tcttcatcccgttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgcc gtcaaaccctgatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctga actttctaaagtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatc cagatcagaagccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatgagaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatca tgtggtgcccgtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaatggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctctggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcgattataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctg ccactgctttgtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaaagctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagc tgccggtcaatccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 5 459 PRT VDVTransfected 293 Cells 5 Met Val Asn Leu Gly Thr Ala Val Arg Ser Leu LeuVal His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile Ser IleSer Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser Asp GlyGly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro Ala LeuSer Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile Leu ValIle Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala Thr AsnTyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly Leu LeuVal Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr Val TrpPro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu Asp ValLeu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile Ser LeuAsp Arg Tyr Val Ala Val Arg Asp Pro 145 150 155 160 Val Glu His Ser ArgPhe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile Val TrpAla Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile Gly LeuArg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 Val LeuAsn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220 PheIle Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230 235240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu 245250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp Gln LysPro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr Met GlnAla Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly Ile ValPhe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe Ile ThrAsn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln Lys LeuMet Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr Val CysSer Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys Ile TyrArg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys Pro AspLys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala Ala ThrAla Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg His ThrAsn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro Gly IleGlu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 Ser AsnVal Val Ser Glu Arg Ile Ser Ser Val 450 455 6 1380 DNA VDV Transfected293 Cells 6 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgc acctaattggcctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatag taactgacacttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtac aaaactggccagcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattc tcgttatcatggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaa tgtccctagccattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttg caattctttatgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcac tagatgtgctattttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggt atgtagcagtgcgtgatcct 480 gttgagcata gccggttcaa ttcgcggact aaggccatca tgaagattgccatcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattg gactgagggacgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccga acttcgttctcatcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatca cctacttcttaacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcaca ccgaggaggaactgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtg atgaggaagagaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaag aaaagcggcctagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtcc ttggcattgtattctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcc tgtcggtgctttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgt ttgtttggattggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaaca aaatttaccgaagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagc ctcctgttcgacagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatg ttaacatttatcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctg gcatagagatgcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcg agaggattagtagtgtgtaa 1380 7 459 PRT VSI Transfected 293 Cells 7 Met Val Asn LeuGly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15 Gly Leu LeuVal Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30 Ile Val ThrAsp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45 Phe Pro AspGly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60 Ile Ile MetThr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 75 80 Met GluLys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 90 95 Ala IleAla Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100 105 110 LeuAla Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys 115 120 125Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser Ile Met 130 135140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Val Arg Ser Pro 145150 155 160 Ile Glu His Ser Arg Phe Asn Ser Arg Thr Lys Ala Ile Met LysIle 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val Ser Val Pro IlePro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val Phe Val Asn AsnThr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val Leu Ile Gly SerPhe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met Val Ile Thr TyrPhe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln Thr Leu Met LeuLeu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn Ile Ser Leu AsnPhe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu Glu Glu Asn AlaPro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg Lys Lys Lys GluLys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn Asn Glu Lys LysAla Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320 Phe Leu IleMet Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330 335 Leu CysGly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340 345 350 ValPhe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val 355 360 365Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg Gln Ile Pro 385390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu Asn Val AsnIle 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg Lys Ala Asn AspThr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn Leu Glu Leu ProVal Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile Ser Ser Val 450455 8 1380 DNA VSI Transfected 293 Cells 8 atggtgaacc tgggcactgcggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcg atatttccataagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtg gacgcttgtttcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtga ttataatcatgacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaaga aactgcacaatgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgg gactacttgtcatgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttac ctagatatttgtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatca tgcacctctgcgccatatcg ctggaccggt atgtagcagt gcgtagtcct 480 attgagcata gccggttcaattcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaa taggagtttcagttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtga ataatactacctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcat tcttcatcccgttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgcc gtcaaaccctgatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctga actttctaaagtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatc cagatcagaagccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatgagaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatca tgtggtgcccgtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaatggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctctggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcgattataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctg ccactgctttgtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaaagctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagc tgccggtcaatccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 9 459 PRT MNITransfected 293 Cells 9 Met Val Asn Leu Gly Thr Ala Val Arg Ser Leu LeuVal His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile Ser IleSer Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser Asp GlyGly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro Ala LeuSer Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile Leu ValIle Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala Thr AsnTyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly Leu LeuVal Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr Val TrpPro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu Asp ValLeu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile Ser LeuAsp Arg Tyr Val Ala Met Arg Asn Pro 145 150 155 160 Ile Glu His Ser ArgPhe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile Val TrpAla Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile Gly LeuArg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 Val LeuAsn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220 PheIle Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230 235240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu 245250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp Gln LysPro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr Met GlnAla Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly Ile ValPhe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe Ile ThrAsn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln Lys LeuMet Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr Val CysSer Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys Ile TyrArg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys Pro AspLys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala Ala ThrAla Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg His ThrAsn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro Gly IleGlu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 Ser AsnVal Val Ser Glu Arg Ile Ser Ser Val 450 455 10 1380 DNA MNI Transfected293 Cells 10 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgc acctaattggcctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatag taactgacacttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtac aaaactggccagcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattc tcgttatcatggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaa tgtccctagccattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttg caattctttatgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcac tagatgtgctattttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggt atgtagcaatgcgtaatcct 480 attgagcata gccggttcaa ttcgcggact aaggccatca tgaagattgccatcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattg gactgagggacgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccga acttcgttctcatcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatca cctacttcttaacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcaca ccgaggaggaactgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtg atgaggaagagaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaag aaaagcggcctagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtcc ttggcattgtattctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcc tgtcggtgctttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgt ttgtttggattggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaaca aaatttaccgaagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagc ctcctgttcgacagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatg ttaacatttatcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctg gcatagagatgcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcg agaggattagtagtgtgtaa 1380 11 459 PRT INV Transfected 293 Cells 11 Met Val Asn LeuGly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15 Gly Leu LeuVal Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30 Ile Val ThrAsp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45 Phe Pro AspGly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60 Ile Ile MetThr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 75 80 Met GluLys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 90 95 Ala IleAla Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100 105 110 LeuAla Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys 115 120 125Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser Ile Met 130 135140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Ile Arg Asn Pro 145150 155 160 Val Glu His Ser Arg Phe Asn Ser Arg Thr Lys Ala Ile Met LysIle 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val Ser Val Pro IlePro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val Phe Val Asn AsnThr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val Leu Ile Gly SerPhe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met Val Ile Thr TyrPhe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln Thr Leu Met LeuLeu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn Ile Ser Leu AsnPhe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu Glu Glu Asn AlaPro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg Lys Lys Lys GluLys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn Asn Glu Lys LysAla Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320 Phe Leu IleMet Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330 335 Leu CysGly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340 345 350 ValPhe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val 355 360 365Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg Gln Ile Pro 385390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu Asn Val AsnIle 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg Lys Ala Asn AspThr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn Leu Glu Leu ProVal Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile Ser Ser Val 450455 12 1380 DNA INV Transfected 293 Cells 12 atggtgaacc tgggcactgcggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcg atatttccataagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtg gacgcttgtttcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtga ttataatcatgacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaaga aactgcacaatgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgg gactacttgtcatgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttac ctagatatttgtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatca tgcacctctgcgccatatcg ctggaccggt atgtagcaat acgtaatcct 480 gttgagcata gccggttcaattcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaa taggagtttcagttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtga ataatactacctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcat tcttcatcccgttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgcc gtcaaaccctgatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctga actttctaaagtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatc cagatcagaagccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatgagaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatca tgtggtgcccgtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaatggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctctggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcgattataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctg ccactgctttgtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaaagctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagc tgccggtcaatccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 13 459 PRT MDVTransfected 293 Cells 13 Met Val Asn Leu Gly Thr Ala Val Arg Ser Leu LeuVal His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile Ser IleSer Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser Asp GlyGly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro Ala LeuSer Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile Leu ValIle Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala Thr AsnTyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly Leu LeuVal Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr Val TrpPro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu Asp ValLeu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile Ser LeuAsp Arg Tyr Val Ala Met Arg Asp Pro 145 150 155 160 Val Glu His Ser ArgPhe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile Val TrpAla Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile Gly LeuArg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 Val LeuAsn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220 PheIle Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230 235240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu 245250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp Gln LysPro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr Met GlnAla Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly Ile ValPhe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe Ile ThrAsn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln Lys LeuMet Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr Val CysSer Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys Ile TyrArg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys Pro AspLys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala Ala ThrAla Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg His ThrAsn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro Gly IleGlu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 Ser AsnVal Val Ser Glu Arg Ile Ser Ser Val 450 455 14 1380 DNA MDV Transfected293 Cells 14 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgc acctaattggcctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatag taactgacacttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtac aaaactggccagcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattc tcgttatcatggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaa tgtccctagccattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttg caattctttatgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcac tagatgtgctattttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggt atgtagcaatgcgtgatcct 480 gttgagcata gccggttcaa ttcgcggact aaggccatca tgaagattgccatcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattg gactgagggacgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccga acttcgttctcatcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatca cctacttcttaacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcaca ccgaggaggaactgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtg atgaggaagagaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaag aaaagcggcctagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtcc ttggcattgtattctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcc tgtcggtgctttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgt ttgtttggattggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaaca aaatttaccgaagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagc ctcctgttcgacagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatg ttaacatttatcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctg gcatagagatgcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcg agaggattagtagtgtgtaa 1380 15 461 PRT MDI Transfected 293 Cells 15 Met Val Asn LeuGly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15 Gly Leu LeuVal Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30 Ile Val ThrAsp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45 Phe Pro AspGly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60 Ile Ile MetThr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 75 80 Met GluLys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 90 95 Ala IleAla Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100 105 110 LeuAla Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys 115 120 125Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser Ile Met 130 135140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Met Arg Asp Pro 145150 155 160 Ile Leu Glu Glu His Ser Arg Phe Asn Ser Arg Thr Lys Ala IleMet 165 170 175 Lys Ile Ala Ile Val Trp Ala Ile Ser Ile Gly Val Ser ValPro Ile 180 185 190 Pro Val Ile Gly Leu Arg Asp Glu Ser Lys Val Phe ValAsn Asn Thr 195 200 205 Thr Cys Val Leu Asn Asp Pro Asn Phe Val Leu IleGly Ser Phe Val 210 215 220 Ala Phe Phe Ile Pro Leu Thr Ile Met Val IleThr Tyr Phe Leu Thr 225 230 235 240 Ile Tyr Val Leu Arg Arg Gln Thr LeuMet Leu Leu Arg Gly His Thr 245 250 255 Glu Glu Glu Leu Arg Asn Ile SerLeu Asn Phe Leu Lys Cys Cys Cys 260 265 270 Lys Lys Gly Asp Glu Glu GluAsn Ala Pro Asn Pro Asn Pro Asp Gln 275 280 285 Lys Pro Arg Arg Lys LysLys Glu Lys Arg Pro Arg Gly Thr Met Gln 290 295 300 Ala Ile Asn Asn GluLys Lys Ala Ser Lys Val Leu Gly Ile Val Phe 305 310 315 320 Phe Val PheLeu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu 325 330 335 Ser ValLeu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu 340 345 350 LeuAsn Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro 355 360 365Leu Val Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys 370 375380 Tyr Leu Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg Gln 385390 395 400 Ile Pro Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu AsnVal 405 410 415 Asn Ile Tyr Arg His Thr Asn Glu Arg Val Val Arg Lys AlaAsn Asp 420 425 430 Thr Glu Pro Gly Ile Glu Met Gln Val Glu Asn Leu GluLeu Pro Val 435 440 445 Asn Pro Ser Asn Val Val Ser Glu Arg Ile Ser SerVal 450 455 460 16 1380 DNA MDI Transfected 293 Cells 16 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcaat gcgtgatcct 480 attgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 17 459 PRTMGV Transfected 293 Cells 17 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Met Arg Gly Pro 145 150 155 160 Val Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 18 1380 DNA MGVTransfected 293 Cells 18 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcaat gcgtggtcct 480 gttgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 19 459 PRT MGI Transfected 293 Cells 19 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Met ArgGly Pro 145 150 155 160 Ile Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 20 1380 DNA MGI Transfected 293 Cells 20 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcaat gcgtggtcct 480 attgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 21 459 PRTMNV Transfected 293 Cells 21 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Met Arg Asn Pro 145 150 155 160 Val Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 22 1380 DNA MNVTransfected 293 Cells 22 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcaat gcgtaatcct 480 gttgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 23 459 PRT IDV Transfected 293 Cells 23 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Ile ArgAsp Pro 145 150 155 160 Val Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 24 1380 DNA IDV Transfected 293 Cells 24 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcaat acgtgatcct 480 gttgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 25 459 PRTIDI Transfected 293 Cells 25 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Ile Arg Asp Pro 145 150 155 160 Ile Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 26 1380 DNA IDITransfected 293 Cells 26 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcaat acgtgatcct 480 attgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 27 459 PRT IGV Transfected 293 Cells 27 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Ile ArgGly Pro 145 150 155 160 Val Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 28 1380 DNA IGV Transfected 293 Cells 28 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcaat acgtggtcct 480 gttgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 29 459 PRTIGI Transfected 293 Cells 29 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Ile Arg Gly Pro 145 150 155 160 Ile Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 30 1380 DNA IGITransfected 293 Cells 30 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcaat acgtggtcct 480 attgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 31 459 PRT INI Transfected 293 Cells 31 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Ile ArgAsn Pro 145 150 155 160 Ile Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 32 1380 DNA INI Transfected 293 Cells 32 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcaat acgtaatcct 480 attgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 33 459 PRTVDI Transfected 293 Cells 33 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Val Arg Asp Pro 145 150 155 160 Ile Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 34 1380 DNA VDITransfected 293 Cells 34 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcagt acgtgatcct 480 attgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 35 459 PRT VGV Transfected 293 Cells 35 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Val ArgGly Pro 145 150 155 160 Val Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 36 1380 DNA VGV Transfected 293 Cells 36 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcagt acgtggtcct 480 gttgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 37 459 PRTVGI Transfected 293 Cells 37 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Val Arg Gly Pro 145 150 155 160 Ile Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 38 1380 DNA VGITransfected 293 Cells 38 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcagt acgtggtcct 480 attgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 39 459 PRT VNI Transfected 293 Cells 39 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Val ArgAsn Pro 145 150 155 160 Ile Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 40 1380 DNA VNI Transfected 293 Cells 40 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcagt acgtaatcct 480 attgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 41 459 PRTMSV Transfected 293 Cells 41 Met Val Asn Leu Gly Thr Ala Val Arg Ser LeuLeu Val His Leu Ile 1 5 10 15 Gly Leu Leu Val Trp Gln Phe Asp Ile SerIle Ser Pro Val Ala Ala 20 25 30 Ile Val Thr Asp Thr Phe Asn Ser Ser AspGly Gly Arg Leu Phe Gln 35 40 45 Phe Pro Asp Gly Val Gln Asn Trp Pro AlaLeu Ser Ile Val Val Ile 50 55 60 Ile Ile Met Thr Ile Gly Gly Asn Ile LeuVal Ile Met Ala Val Ser 65 70 75 80 Met Glu Lys Lys Leu His Asn Ala ThrAsn Tyr Phe Leu Met Ser Leu 85 90 95 Ala Ile Ala Asp Met Leu Val Gly LeuLeu Val Met Pro Leu Ser Leu 100 105 110 Leu Ala Ile Leu Tyr Asp Tyr ValTrp Pro Leu Pro Arg Tyr Leu Cys 115 120 125 Pro Val Trp Ile Ser Leu AspVal Leu Phe Ser Thr Ala Ser Ile Met 130 135 140 His Leu Cys Ala Ile SerLeu Asp Arg Tyr Val Ala Met Arg Ser Pro 145 150 155 160 Val Glu His SerArg Phe Asn Ser Arg Thr Lys Ala Ile Met Lys Ile 165 170 175 Ala Ile ValTrp Ala Ile Ser Ile Gly Val Ser Val Pro Ile Pro Val 180 185 190 Ile GlyLeu Arg Asp Glu Ser Lys Val Phe Val Asn Asn Thr Thr Cys 195 200 205 ValLeu Asn Asp Pro Asn Phe Val Leu Ile Gly Ser Phe Val Ala Phe 210 215 220Phe Ile Pro Leu Thr Ile Met Val Ile Thr Tyr Phe Leu Thr Ile Tyr 225 230235 240 Val Leu Arg Arg Gln Thr Leu Met Leu Leu Arg Gly His Thr Glu Glu245 250 255 Glu Leu Arg Asn Ile Ser Leu Asn Phe Leu Lys Cys Cys Cys LysLys 260 265 270 Gly Asp Glu Glu Glu Asn Ala Pro Asn Pro Asn Pro Asp GlnLys Pro 275 280 285 Arg Arg Lys Lys Lys Glu Lys Arg Pro Arg Gly Thr MetGln Ala Ile 290 295 300 Asn Asn Glu Lys Lys Ala Ser Lys Val Leu Gly IleVal Phe Phe Val 305 310 315 320 Phe Leu Ile Met Trp Cys Pro Phe Phe IleThr Asn Ile Leu Ser Val 325 330 335 Leu Cys Gly Lys Ala Cys Asn Gln LysLeu Met Glu Lys Leu Leu Asn 340 345 350 Val Phe Val Trp Ile Gly Tyr ValCys Ser Gly Ile Asn Pro Leu Val 355 360 365 Tyr Thr Leu Phe Asn Lys IleTyr Arg Arg Ala Phe Ser Lys Tyr Leu 370 375 380 Arg Cys Asp Tyr Lys ProAsp Lys Lys Pro Pro Val Arg Gln Ile Pro 385 390 395 400 Arg Val Ala AlaThr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn Ile 405 410 415 Tyr Arg HisThr Asn Glu Arg Val Val Arg Lys Ala Asn Asp Thr Glu 420 425 430 Pro GlyIle Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro 435 440 445 SerAsn Val Val Ser Glu Arg Ile Ser Ser Val 450 455 42 1380 DNA MSVTransfected 293 Cells 42 atggtgaacc tgggcactgc ggtgcgctca ctccttgtgcacctaattgg cctattggtt 60 tggcagttcg atatttccat aagtccagta gcagctatagtaactgacac ttttaattcc 120 tccgatggtg gacgcttgtt tcaattcccg gacggggtacaaaactggcc agcactttca 180 atagtcgtga ttataatcat gacaataggg ggcaacattctcgttatcat ggcagtaagc 240 atggagaaga aactgcacaa tgctaccaat tatttcttaatgtccctagc cattgctgat 300 atgctggtgg gactacttgt catgcccctg tctctgcttgcaattcttta tgattatgtc 360 tggcctttac ctagatattt gtgccccgtc tggatttcactagatgtgct attttcaact 420 gcgtccatca tgcacctctg cgccatatcg ctggaccggtatgtagcaat gcgtagtcct 480 gttgagcata gccggttcaa ttcgcggact aaggccatcatgaagattgc catcgtttgg 540 gcaatatcaa taggagtttc agttcctatc cctgtgattggactgaggga cgaaagcaaa 600 gtgttcgtga ataatactac ctgcgtgctc aatgacccgaacttcgttct catcgggtcc 660 ttcgtggcat tcttcatccc gttgacaatt atggtgatcacctacttctt aacgatctac 720 gtcctacgcc gtcaaaccct gatgttactt cgaggtcacaccgaggagga actgcgtaat 780 atcagcctga actttctaaa gtgctgctgc aagaagggtgatgaggaaga gaacgctccc 840 aaccccaatc cagatcagaa gccacgtcga aagaagaaagaaaagcggcc tagaggcacc 900 atgcaagcta tcaacaatga gaagaaagct tccaaagtccttggcattgt attctttgtg 960 tttctgatca tgtggtgccc gtttttcatc accaatatcctgtcggtgct ttgtgggaag 1020 gcctgtaacc aaaagctaat ggagaaactt ctcaatgtgtttgtttggat tggctatgtg 1080 tgttcaggca tcaatcctct ggtgtacact ctcttcaacaaaatttaccg aagggctttc 1140 tctaaatatt tgcgctgcga ttataagcca gacaaaaagcctcctgttcg acagattcct 1200 agggttgctg ccactgcttt gtctgggagg gagctcaatgttaacattta tcggcatacc 1260 aatgaacgtg tagttaggaa agctaatgac acagagcctggcatagagat gcaggtagag 1320 aatttagagc tgccggtcaa tccctctaat gtggtcagcgagaggattag tagtgtgtaa 1380 43 459 PRT MSI Transfected 293 Cells 43 MetVal Asn Leu Gly Thr Ala Val Arg Ser Leu Leu Val His Leu Ile 1 5 10 15Gly Leu Leu Val Trp Gln Phe Asp Ile Ser Ile Ser Pro Val Ala Ala 20 25 30Ile Val Thr Asp Thr Phe Asn Ser Ser Asp Gly Gly Arg Leu Phe Gln 35 40 45Phe Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser Ile Val Val Ile 50 55 60Ile Ile Met Thr Ile Gly Gly Asn Ile Leu Val Ile Met Ala Val Ser 65 70 7580 Met Glu Lys Lys Leu His Asn Ala Thr Asn Tyr Phe Leu Met Ser Leu 85 9095 Ala Ile Ala Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu 100105 110 Leu Ala Ile Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys115 120 125 Pro Val Trp Ile Ser Leu Asp Val Leu Phe Ser Thr Ala Ser IleMet 130 135 140 His Leu Cys Ala Ile Ser Leu Asp Arg Tyr Val Ala Met ArgSer Pro 145 150 155 160 Ile Glu His Ser Arg Phe Asn Ser Arg Thr Lys AlaIle Met Lys Ile 165 170 175 Ala Ile Val Trp Ala Ile Ser Ile Gly Val SerVal Pro Ile Pro Val 180 185 190 Ile Gly Leu Arg Asp Glu Ser Lys Val PheVal Asn Asn Thr Thr Cys 195 200 205 Val Leu Asn Asp Pro Asn Phe Val LeuIle Gly Ser Phe Val Ala Phe 210 215 220 Phe Ile Pro Leu Thr Ile Met ValIle Thr Tyr Phe Leu Thr Ile Tyr 225 230 235 240 Val Leu Arg Arg Gln ThrLeu Met Leu Leu Arg Gly His Thr Glu Glu 245 250 255 Glu Leu Arg Asn IleSer Leu Asn Phe Leu Lys Cys Cys Cys Lys Lys 260 265 270 Gly Asp Glu GluGlu Asn Ala Pro Asn Pro Asn Pro Asp Gln Lys Pro 275 280 285 Arg Arg LysLys Lys Glu Lys Arg Pro Arg Gly Thr Met Gln Ala Ile 290 295 300 Asn AsnGlu Lys Lys Ala Ser Lys Val Leu Gly Ile Val Phe Phe Val 305 310 315 320Phe Leu Ile Met Trp Cys Pro Phe Phe Ile Thr Asn Ile Leu Ser Val 325 330335 Leu Cys Gly Lys Ala Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn 340345 350 Val Phe Val Trp Ile Gly Tyr Val Cys Ser Gly Ile Asn Pro Leu Val355 360 365 Tyr Thr Leu Phe Asn Lys Ile Tyr Arg Arg Ala Phe Ser Lys TyrLeu 370 375 380 Arg Cys Asp Tyr Lys Pro Asp Lys Lys Pro Pro Val Arg GlnIle Pro 385 390 395 400 Arg Val Ala Ala Thr Ala Leu Ser Gly Arg Glu LeuAsn Val Asn Ile 405 410 415 Tyr Arg His Thr Asn Glu Arg Val Val Arg LysAla Asn Asp Thr Glu 420 425 430 Pro Gly Ile Glu Met Gln Val Glu Asn LeuGlu Leu Pro Val Asn Pro 435 440 445 Ser Asn Val Val Ser Glu Arg Ile SerSer Val 450 455 44 1380 DNA MSI Transfected 293 Cells 44 atggtgaacctgggcactgc ggtgcgctca ctccttgtgc acctaattgg cctattggtt 60 tggcagttcgatatttccat aagtccagta gcagctatag taactgacac ttttaattcc 120 tccgatggtggacgcttgtt tcaattcccg gacggggtac aaaactggcc agcactttca 180 atagtcgtgattataatcat gacaataggg ggcaacattc tcgttatcat ggcagtaagc 240 atggagaagaaactgcacaa tgctaccaat tatttcttaa tgtccctagc cattgctgat 300 atgctggtgggactacttgt catgcccctg tctctgcttg caattcttta tgattatgtc 360 tggcctttacctagatattt gtgccccgtc tggatttcac tagatgtgct attttcaact 420 gcgtccatcatgcacctctg cgccatatcg ctggaccggt atgtagcaat gcgtagtcct 480 attgagcatagccggttcaa ttcgcggact aaggccatca tgaagattgc catcgtttgg 540 gcaatatcaataggagtttc agttcctatc cctgtgattg gactgaggga cgaaagcaaa 600 gtgttcgtgaataatactac ctgcgtgctc aatgacccga acttcgttct catcgggtcc 660 ttcgtggcattcttcatccc gttgacaatt atggtgatca cctacttctt aacgatctac 720 gtcctacgccgtcaaaccct gatgttactt cgaggtcaca ccgaggagga actgcgtaat 780 atcagcctgaactttctaaa gtgctgctgc aagaagggtg atgaggaaga gaacgctccc 840 aaccccaatccagatcagaa gccacgtcga aagaagaaag aaaagcggcc tagaggcacc 900 atgcaagctatcaacaatga gaagaaagct tccaaagtcc ttggcattgt attctttgtg 960 tttctgatcatgtggtgccc gtttttcatc accaatatcc tgtcggtgct ttgtgggaag 1020 gcctgtaaccaaaagctaat ggagaaactt ctcaatgtgt ttgtttggat tggctatgtg 1080 tgttcaggcatcaatcctct ggtgtacact ctcttcaaca aaatttaccg aagggctttc 1140 tctaaatatttgcgctgcga ttataagcca gacaaaaagc ctcctgttcg acagattcct 1200 agggttgctgccactgcttt gtctgggagg gagctcaatg ttaacattta tcggcatacc 1260 aatgaacgtgtagttaggaa agctaatgac acagagcctg gcatagagat gcaggtagag 1320 aatttagagctgccggtcaa tccctctaat gtggtcagcg agaggattag tagtgtgtaa 1380 45 31 DNAArtificial Sequence mouse 45 ctgaagcaat aaatggtgaa cctgggcact g 31 46 32DNA Artificial Sequence mouse 46 gcgtctagat ttcctgtagg aaagctgcgc tg 32

What is claimed is:
 1. A method for identifying ligands of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID Nos. 3, 5, 7, 9 and 11, comprising contacting a molecule or a mixturecontaining different molecules with a recombinant cell expressing at itssurface the polypeptide, under conditions permitting interaction betweenthe polypeptide and the molecule, and detecting molecules bound to thepolypeptide.
 2. A method for identifying modulators of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID Nos. 3, 5, 7, 9 and 11, comprising contacting in the presence of 5-HTa molecule or a mixture containing different molecules with arecombinant cell expressing at its surface the polypeptide, underconditions permitting interaction between the polypeptide and 5-HT, anddetecting molecules capable of modulating the activity of 5-HT withrespect to the polypeptide.